1/9. Menkes disease after copper histidine replacement therapy: case report.Menkes disease (MD) is an X-linked recessive disorder of copper metabolism, characterized in its untreated state by progressive disorders of multiple systems, especially the central nervous system (CNS) and connective tissue, and death by 3 years of age. Recently, therapy with copper-histidine has modified the severity of MD and permitted survival into adolescence. Clinical response has been greater for the neurological abnormalities than for the connective tissue abnormalities. In this report, we describe the postmortem pathology of one individual who had received copper-histidine therapy and died at age 10; we believe this to be the first such pathological report. The postmortem examination demonstrated significant pathology of mesenchymal tissues, including skeletal abnormalities, vascular degeneration, and bladder diverticula. The CNS, by contrast, showed minimal pathology. The phenotype was more consistent with occipital horn syndrome, a milder allelic disorder of copper metabolism, than with classic MD. The differential sensitivity of CNS and mesenchymal tissues to copper-histidine therapy may result from heterogeneity in the response of different copper-dependent enzymes.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |
2/9. Aceruloplasminemia, an inherited disorder of iron metabolism.ceruloplasmin, a multi-copper ferroxidase that affects the distribution of tissue iron, has antioxidant effects through the oxidation of ferrous iron to ferric iron. Aceruloplasminemia is an inherited disorder of iron metabolism due to the complete lack of ceruloplasmin ferroxidase activity caused by mutations in the ceruloplasmin gene. It is characterized by iron accumulation in the brain as well as visceral organs. Clinically, the disease consists of the triad of retinal degeneration, diabetes mellitus, and neurological disease, which include ataxia, involuntary movements, and dementia. These symptoms reflect the sites of iron deposition. The unique involvement of the central nervous system distinguishes aceruloplasminemia from other inherited and acquired iron storage disorders. Twenty-one mutations in the ceruloplasmin gene have been reported in 24 families worldwide. In japan, the incidence was estimated to be approximately one per 2,000,000 in the case of non-consanguineous marriages. Excess iron functions as a potent catalyst of biologic oxidation. Previously we showed that an increased iron concentration is associated with increased levels of lipid peroxidation in the serum, cerebrospinal fluid, and erythrocyte membranes. The levels of malondialdehyde and 4-hydroxynonenals, indicators of lipid peroxidation, were also elevated in the basal ganglia and cerebral cortex. Positron emission tomography showed diminished brain metabolism of glucose and oxygen. Enzyme activities in the mitochondrial respiratory chain of the basal ganglia were reduced to approximate 45% and 42%, respectively, for complexes I and IV. These findings suggest that iron-mediated free radicals causes neuronal cell damage through lipid peroxidation and mitochondrial dysfunction in aceruloplasminemia brains.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |
3/9. Anaesthetic considerations in the child with Menkes' syndrome.The author presents and discusses the anaesthetic implications of a four-month-old infant with Menkes' syndrome who required tracheostomy. Menkes' syndrome is an X-linked recessive disorder of copper absorption and metabolism. Defective processing of copper results in abnormalities of several enzyme systems leading to severe dysfunction of multiple organ systems. Due to the progressive nature of this disorder and its severe effects on several different organ systems, most importantly the central nervous system, these children frequently require anaesthetic care during imaging procedures such as MRI or during various surgical operations. The high prevalence of seizure disorders, gastroesophageal reflux with the risk of aspiration, and airway complications related to poor pharyngeal muscle control are of concern to the anaesthetist. In addition, defective collagen formation, similar to that seen in ehlers-danlos syndrome, may be present. Identification of these associated conditions during the preoperative examination will guide the selection of appropriate, safe anaesthetic care for these children.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |
4/9. Downregulation of myelination, energy, and translational genes in Menkes disease brain.Menkes disease (MD) is an X-linked recessive neurodegenerative disorder caused by mutations in a copper-transporting p-type ATPase (ATP7A) that normally delivers copper to the central nervous system. The precise reasons for neurodegeneration in MD are poorly understood. We hypothesized that gene expression changes in a MD patient with a lethal ATP7A mutation would indicate pathophysiological cascades relevant to the effects of copper deficiency in the developing brain. To test this hypothesis, oligonucleotide probes for 12,000 genes arrayed on Affymetrix Human genome U95 GeneChips were used for expression profiling of fluorescently labeled primary cRNAs from post-mortem cerebral cortex and cerebellum of a MD patient who died at 6 months of age and a normal control brain matched for age, gender, and race. Histopathologic analysis of the proband's brain showed preservation of neuronal integrity and no hypoxic effects. However, cerebrospinal fluid and brain copper levels were subnormal, and expression profiling identified over 350 known dysregulated genes. For a subset of genes (approximately 12%) analyzed by quantitative RT-PCR, the correct cross-validation rate was 88%. Thirty known genes were altered in both cortex and cerebellum. Downregulation of genes involved in myelination, energy metabolism, and translation was the major finding. The cerebellum was more sensitive to copper deficiency.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |
5/9. Correction of cerebrospinal fluid copper in Menkes kinky hair disease.A patient with Menkes Kinky hair disease was treated with infusions of copper-histidine which resulted in normal copper values in the cerebrospinal fluid. This tends to confirm the in vitro data that copper is transported into the central nervous system complexed with histidine or other similar ligands.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |
6/9. Generalized giant axonal neuropathy: a filament-forming disease of neuronal, endothelial, glial, and schwann cells in a patient without kinky hair.The process of giant axonal neuropathy (GAN) is not restricted to the peripheral nerves, but also involves the central nervous system. In a 25 year old man with normal hair, abundant axon swellings and spheroids were observed in the spinal cord, brain system, and cerebral cortex. The findings in the sural nerve have already been published by Boltshauser et al. (1977). Accumulations of filaments in the axons and in the perineural cells were accompanied by Rosenthal fibres. The ultrastructural pattern of GAN differs clearly from that of neuroaxonal dystrophies.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |
7/9. An autopsy case of Menkes kinky hair disease.An autopsy cases of Menkes kinky hair disease in a 1 year and 8 months old male infant is presented and compared with the morphological findings of the previous literatures. The main pathological changes are atrophy of the whole cerebellar cortex and bilateral temporal lobe, atrophy with demyelination of the white matter, tortuous running of the cerebral arteries, multiple diverticulosis of the urinary bladder and hyaline-like deposition in the gastric submucosa. Microscopically, the peculiar degenerative change of Purkinje cell (somal sprout) is the only characteristic lesion in our case and the others. It is suggested that Menkes kinky hair disease may be a syndrome due to metabolic disturbance appearing not only in ectoderm such as the central nervous system, but also in mesoderm such as connective tissue and bone.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |
8/9. An X-linked disease of the nervous system with disordered copper metabolism and features differing from Menkes disease.We studied 2 of 4 affected boys with a new disease associated with abnormalities of copper metabolism. The four cases occurred in two generations of a family. This syndrome was similar to Menkes disease in some respects: X-linked recessive inheritance, marked psychomotor retardation with seizures, low serum copper and ceruloplasmin levels, and a block in gut copper absorption. There were also striking differences from Menkes disease. patients had normal birthweight at term, no hypothermia, and survived beyond the usual Menkes age group with static neurologic disease including hypotonia and choreoathetosis. In addition, general examination of both children was unremarkable apart from undescended testes and growth retardation. The hair, facies, and skin were normal and there was no radiologic evidence of bony changes. Detailed studies of copper absorption were performed.- - - - - - - - - - ranking = 1.3850048439832keywords = nervous system (Clic here for more details about this article) |
9/9. Cytochrome C oxidase deficiency and neuronal involvement in Menkes' kinky hair disease: immunohistochemical study.antibodies against subunits II and IV of cytochrome c oxidase (COX) and against complex III of the respiratory chain were used to study the expression of these proteins in the cerebellum, spinal cord, and other regions of the central nervous system in an autoptic case of Menkes' kinky hair disease (MKHD). We found a reduced expression of COX subunits in all examined areas whereas staining for complex III appeared normal. Immunostaining was altered in morphologically well-preserved neurons, suggesting that COX deficiency may have a pathogenetic role in the neuronal degeneration of MKHD.- - - - - - - - - - ranking = 1keywords = central nervous system, nervous system (Clic here for more details about this article) |